tbuckley/cabot-search huggingface dataset:
Abstract 2536: Intracellular Ctla4 overexpression promotes melanoma progression and metastasis
Authors: Hasan Raza Kazmi, Xuan Mo, Bo Zhou, Sarah Preston Alp, Scott Gross, Hassaan Wajeeh, Carmen Merali, John Elrod, Jonathan Soboloff, Salim Merali, M. Raza Zaidi
Journal: Cancer Research (2023)

Abstract Cytotoxic T Lymphocyte Antigen 4 (CTLA4) expressed on the surface of T cells is an important immunotherapeutic target in many cancers, including melanoma. However, we previously found highly upregulated expression of CTLA4 in BRAF/NRAS-mutant human melanoma cell lines and tissues. Although CTLA4 is almost entirely expressed intracellularly in melanoma cells, its intracellular functions have remained elusive. Ectopic expression of Ctla4 (Ctla4-ee) in mouse melanoma cell lines significantly promoted lung colonization in syngeneic mice as well as in immunocompromised mice, suggesting that Ctla4 had pro-tumorigenic effects independent of its extracellular immune checkpoint function. Proteomics analysis identified apoptosis to be a major affected pathway and we found that Ctla4 ectopic-expressing mouse melanoma cells (B2905-Ctla4-ee) were significantly resistant to doxorubicin-induced apoptosis as compared to empty vector (EV) controls. In a reciprocal experiment, knocking out CTLA4 in the Hs936T human melanoma cells, that exhibit high endogenous CTLA4 expression, showed significantly increased apoptosis than the parental cells. Moreover, significant upregulation of anti-apoptotic proteins (Bnip3, Birc6, Pak1, Mcl-1, Survivin, Rac1/Cdc42, Bcl-2, and Bnip3l) and downregulation of pro-apoptotic proteins (p53 and Bad) were observed in CTLA4-ee cells as compared to EV controls. CTLA4-ee cells also showed significantly higher invasion in Matrigel-coated Transwell assay. Interestingly, we also found that CTLA4 translocated to mitochondria, where it downregulated oxidative phosphorylation and increased glycolysis. These findings lead us to hypothesize that CTLA4 plays a significant role in regulating apoptosis and mitochondrial metabolic functions, leading to the promotion of melanoma progression and metastasis. Citation Format: Hasan Raza Kazmi, Xuan Mo, Bo Zhou, Sarah Preston Alp, Scott Gross, Hassaan Wajeeh, Carmen Merali, John Elrod, Jonathan Soboloff, Salim Merali, M. Raza Zaidi. Intracellular Ctla4 overexpression promotes melanoma progression and metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2536.
Abstract 2385: Targeting mannose receptor expression on macrophages for sentinel lymph node mapping in endometrial cancer: murine model
Authors: Hyun-Woong Cho, OK Hwa Jeon, Sanghoon Lee, Hyun Koo Kim, Jae Kwan Lee, Jin Hwa Hong
Journal: Cancer Research (2023)

Abstract Background: Sentinel lymph node (SLN) mapping has been used in various cancer surgery including endometrial cancer as a targeted assessment tool for identifying lymph node metastases, an alternative for complete lymphadenectomy to minimize surgical morbidity. Neomannosyl human serum albumin (MSA) targets the macrophage mannose receptor CD206 which is highly expressed in metastatic lymph node. The aim of this study was to evaluate the effectiveness of indocyanine green-neomannosyl human serum albumin (MSA:ICG) which targets macrophage mannose receptor CD206 for SLN mapping. Methods: LN targeting ability was examined on mouse footpad models of uterine cancer using MSA:ICG and ICG for comparison. Seven mice with uterine cancer and 2 mice without cancer as a control group were each assigned to MSA:ICG and ICG groups. After injection of tracers, fluorescence images were taken and SLN biopsy was done to confirm LN metastasis status. We compared the signal-to-background ratio (SBR) according to time. Results: In both MSA:ICG and ICG group, 16 lymph nodes out of 18 were detected using fluorescence imaging (detection rate: 88.9%). Four lymph nodes in MSA:ICG group and 5 lymph nodes in ICG group were metastatic among 16 lymph node each group. Excluding lymph nodes that were not detected, the SBR after the injection of MSA:ICG group was significantly higher than ICG group in metastatic LN (MSA:ICG 4.36 vs ICG 3.07, p&amp;lt;0.001), non-metastatic lymph nodes (MSA:ICG 3.11 vs ICG 1.93, p=0.001), and normal control lymph nodes (MSA:ICG 1.38 vs ICG 0.54, p&amp;lt;0.001). Comparing signal intensity according to CD206 expression, there was no difference in SBR values between the two groups in patients without CD206 expression, but the MSA group had a statistically significantly higher SBR value than the ICG group (p&amp;lt;0.001) in patients with CD206 moderate or high expression. Conclusions: This study showed that MSA:ICG may be an effective tracer for sentinel lymph node mapping. In addition, the metastatic lymph nodes expressing CD206 showed higher signal than normal lymph nodes in MSA:ICG group, unlike in ICG group. Further studies using larger animal models and clinical trials are needed to confirm this result. Citation Format: Hyun-Woong Cho, OK Hwa Jeon, Sanghoon Lee, Hyun Koo Kim, Jae Kwan Lee, Jin Hwa Hong. Targeting mannose receptor expression on macrophages for sentinel lymph node mapping in endometrial cancer: murine model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2385.
Abstract 6515: Pancreatic ductal adenocarcinoma (PDAC) early detection
Authors: Juan P. Hinestrosa, Harmeet Dhani, Gregor Schroeder, Jean M. Lewis, Heath I. Balcer, Razelle Kurzrock, Dove Keith, Rosalie Sears, Paul Billings
Journal: Cancer Research (2023)

Abstract Introduction Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer and is one of the deadliest cancer in the U.S., with a 5-year survival rate of just 11%. It is expected that ~62,000 new cases will be diagnosed in the US in 2023 and &amp;gt;70% of those will be at the regional or distant state, when curative resection is no longer an option. It is imperative that tools enabling early disease detection (stages I and II) are developed to improve patient survival outcomes. Here, we report the results of a study on the utility of extracellular vesicles (EVs) for early PDAC detection. Methods Our case-control training set was comprised of 75 pathologically confirmed PDAC cases (Stage I = 31, Stage II = 44) and 640 controls (including 11 subjects with pancreatitis) for EV biomarker and algorithm selection via machine learning. EVs from plasma were isolated using a proprietary technology, then EV-bound proteins of interest were analyzed via an immunoassay. A second independently collected cohort of 20 confirmed PDAC cases (Stage I = 10, Stage II = 10) and 27 controls (including 9 patients newly diagnosed with diabetes) was used for validation. Results The machine learning analysis using EV-isolated proteins generated a signature that utilized 8 different biomarkers, with an AUC of 0.989 (95% CI: 0.980 - 0.998) in the training set and an AUC of 0.987 (CI: 0.964 - 1.000) in the validation set. For the validation set, the sensitivity was 95% (CI: 76.4% - 99.1%) and the specificity was 92.6% (CI: 76.6% - 97.9%), with 10 out of 10 stage I cases and 9 out of 10 stage II cases correctly classified. Conclusions The ability to alter the future outcomes of PDAC patients will be predicated on development of a new generation of early-detection biomarkers and technologies. The use of EV protein signatures, a new class of cell-free biomarker, permits detection at high sensitivity and specificity, as demonstrated for the independently collected validation cohort. Studies aimed to assess this test for high-risk patients (family history of PDAC, known germline mutations, precursor lesions, hereditary pancreatitis, new onset diabetes will continue towards the establishment of real-world evidence. Citation Format: Juan P. Hinestrosa, Harmeet Dhani, Gregor Schroeder, Jean M. Lewis, Heath I. Balcer, Razelle Kurzrock, Dove Keith, Rosalie Sears, Paul Billings. Pancreatic ductal adenocarcinoma (PDAC) early detection. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6515.
Abstract 1775: Expansion of human T cells using xenogeneic free and gamma irradiated human platelet lysate
Authors: Vanesa Alonso-Camino
Journal: Cancer Research (2023)

Abstract Commercially available human platelet lysate (hPL) is produced using expired human platelets obtained from accredited blood banks in the United States. These platelets were originally intended for use in patient transfusion. The safety of platelets used in transfusion is managed by the U.S. Food &amp; Drug Administration (FDA), as well as the American Association of Blood Banks (AABB). These organizations set standards, including testing for transmissible diseases. The United States record for blood safety is well established, with extremely low rates of disease transmission, making the platelet units used for hPL manufacture low risk. The Covid-19 pandemic has increased awareness of emerging infectious diseases, even though transmission of Covid-19 via blood transfusion has not been documented. For that reason, gamma irradiated hPL offers an additional safety measure in the clinic. Chimeric Antigen Receptor (CAR) expressing T-cells have demonstrated potent clinical efficacy in patients with hematological malignancies. In addition, there are several phase I clinical trials evaluating the use of CAR-T-cells for targeting of solid tumor-associated antigens. Some of the challenging issues found during production of CAR-T cells are the efficiency of T cell transduction to generate CAR-T cells, the expansion of T cells to clinically relevant numbers and the long-term survival in vivo of the therapeutic cells. The use of human platelet lysate has been demonstrated to improve these issues. Our data from experiments performed using human CD3+ from donors demonstrates that human platelet lysates offer an improved performance on T cell expansion versus serum derived products. hPL efficiently promotes T cell expansion, with higher cell yields and lower cell exhaustion rate. Additionally, we efficiently developed a protocol for suspension culture of T cells, which could facilitate the large-scale expansion of allogeneic CAR-T cells. Citation Format: Vanesa Alonso-Camino. Expansion of human T cells using xenogeneic free and gamma irradiated human platelet lysate [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1775.
Abstract 13: A non-surgical approach to develop an orthotopic colorectal cancer mouse model
Authors: Samantha Sharma, Kevin Van der Jeught, Zhuolong Zhou, Xinna Zhang, Xiongbin Lu
Journal: Cancer Research (2023)

Abstract Recapitulating physiologically relevant tumor microenvironment is an important yet a significant challenge in modeling colorectal cancer (CRC) for basic and translational studies. Cecal-wall injection is most widely used for orthotopic animal models of CRC. However, this procedure involves complicated surgical procedures, and its ectotopic nature is a major issue for therapeutic development. Here, we report a non-surgical procedure for establishing orthotopic CRC mouse models, reflecting the appropriate tumor microenvironment to better model the disease development and facilitate translational studies, including drug identification and validation. For this procedure, the mice are fasted overnight. The following day, anesthesia is induced in the study mice (Balb/c or C57BL/6) while placed on a thermostat-controlled heating blanket. Next, a specialized catheter is inserted and distended into the mouse colon to gently block the colon and ensure the localization for tumor development. Hereafter, the colonic epithelium is treated with proteases and mechanical abrasion to cause mild disruption. Following the local gut inflammation, the targeted colon region is incubated with tumor cells, leading to the adhesion of tumor cells (CT26 or MC38) to the colonic epithelium. Based on the animal background and the cell line used, the tumor is developed within 4-6 weeks. Pathological assessment on hematoxylin and eosin stained tumor tissues confirmed the stages of tumor development. Additional adaptations of this procedure include i) tumor development in different mouse strains, ii) local delivery of adeno-Cre in transgenic mice for CRC, and iii) transplantation of tumor organoids in the mouse colon. Overall, our non-surgical procedure overcomes the technical difficulties of surgery and offers several advantages like ease of handling, cost-effectiveness, pain-free with nearly no procedure-associated mortality, and adaptability to several strains. To conclude, this non-surgical procedure is a novel and promising alternative to conventional orthotopic CRC mouse models for translational studies. Citation Format: Samantha Sharma, Kevin Van der Jeught, Zhuolong Zhou, Xinna Zhang, Xiongbin Lu. A non-surgical approach to develop an orthotopic colorectal cancer mouse model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 13.
Abstract 1089: High grade serous ovarian cancer: Detecting stemness and EMT levels in response to chemo and radiation therapy
Authors: Yeonkyu Jung, Aaron Keniston, Ashley Antonissen, Ann Morcos, Antonella Bertucci, Marcelo Vazquez, Juli Unternaehrer
Journal: Cancer Research (2023)

Abstract High-Grade Serous Ovarian Cancer (HGSOC) is the most fatal of gynecological cancers. The recurrence rate of HGSOC after treatment is more than 80%. The available treatment options for HGSOC are limited; standard of care includes surgery combined with chemotherapy, with radiation therapy in some advanced cases. Both chemotherapy and radiation therapy are known to induce tumor cell aggressiveness. Many cancer studies have demonstrated that cancer stem cells (CSCs) and the epithelial-mesenchymal transition (EMT) promote cancer aggressiveness, invasion, metastasis, and drug resistance. Therefore, to better understand the cause of the poor prognosis in HGSOC, our objective is to scrutinize the role of CSCs and EMT in chemo- and radiation resistance. To lead our inquiry, we utilized the SORE6 reporter to identify Sox2/Oct4 expression, which indicates the stemness, and the Zeb1 3’ UTR reporter to detect EMT. Using flow cytometry, we quantified the reporter activity in 10 ovarian cancer cell types, including chemo-sensitive and chemo-resistant ones, considering both cell lines and patient-derived cells. Chemo-resistant cells are grown under cisplatin treatment. We exposed some of these ovarian cancer cell lines to 0, 1, 2, 4 and 8Gy of 250 MeV proton and 6 MeV photon beams, then analyzed the reporter activity 72 hours post-radiation. Our findings exhibit that chemo-resistant cells express higher stemness and EMT levels than chemo-sensitive cells and have higher resistance to radiation. These reporters can detect radiation-induced stemness and EMT. Furthermore, stemness and EMT levels positively correlate with the radiation dosage increment. We conclude that these reporters are an efficient surrogate for detection of stemness and EMT and can be used to test strategies for prevention of therapy-induced aggressive phenotypes. Citation Format: Yeonkyu Jung, Aaron Keniston, Ashley Antonissen, Ann Morcos, Antonella Bertucci, Marcelo Vazquez, Juli Unternaehrer. High grade serous ovarian cancer: Detecting stemness and EMT levels in response to chemo and radiation therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1089.
Abstract 2715: Utilizing a pH sensitive peptide (pHLIP) for tumor targeted delivery of an immunogenic peptide motif
Authors: Annali M. Yurkevicz, Yanfeng Liu, Peter M. Glazer
Journal: Cancer Research (2023)

Abstract Chimeric antigen receptor (CAR) T cell and immune-cell therapies are revolutionizing how patients are treated in the clinic by targeting tumor-specific antigens. Specifically, advances in antigen targeting of CD20 and CD19 with CAR T cell therapy has increased overall survival of this patient population and has influenced to expand T cell repertoire to novel antigen targets. However, limitations to these cell-based therapies are the lack of development against solid tumor antigens, partly due to the paucity of antigen candidates that are sufficiently specific to epithelial cancers. Therefore, technologies that can mark tumor cells for immune recognition could prove beneficial in the treatment of these solid cancers. This project aims to artificially deliver an antigen to tumor cells by harnessing a universal property of tumors: acidic microenvironment. The pH low insertion peptide (pHLIP) is a technology that targets solid tumors based on the low pH produced by the Warburg effect. pHLIP-conjugates have undergone extensive development for drug delivery, with one notable candidate CBX12 entering phase I clinical trials in 2021. Our system uses a pHLIP-conjugated SIINFEKL peptide (derived from ovalbumin) to serve as our model antigen system, with SIINFEKL-targeting T cells (OT1) that can be used as a tool to investigate antigen delivery, recognition, and functionality. We have observed through immunofluorescence that B16 F10 mouse melanoma cells treated in vitro with the 1uM pHLIP-SIINFEKL construct under acidic conditions can recruit OT1 cells and induce a T cell synapse. Preliminary in vivo experiments in C57BL/6-Tg OT1 mice bearing B16 F10 flank tumors showed that treatment with pHLIP-SIINFEKL by intravenous administration led to a suppression of tumor growth compared to controls, with approximately 50% smaller fold change in tumor volume. Cumulatively, these initial results suggest that pHLIP-SIINFEKL can be delivered to tumors to recruit OT1 cells to engage in antigen recognition and lead to efficacy in tumor growth delay in vivo. This technology has the capability to provide a novel approach to decorate solid tumors with engineered antigens for enhanced immune recognition and anti-tumor efficacy. Citation Format: Annali M. Yurkevicz, Yanfeng Liu, Peter M. Glazer. Utilizing a pH sensitive peptide (pHLIP) for tumor targeted delivery of an immunogenic peptide motif [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2715.
Abstract 2712: Killing cancer stem cells in 72 hours can cure breast cancer
Authors: Keum-soo Song, Satish Balasaheb Nimse, Taisun Kim
Journal: Cancer Research (2023)

Abstract Advancements in stem cell technology can open new doors for treating various diseases, disorders, and disabilities, including cardiovascular diseases, gastrointestinal diseases, liver diseases, arthritis, neurological disorder, and baldness. Though stem cell technology offers several answers to treat these ailments, the success of this technology is unfortunately daunted by the development of stem cells into cancer stem cells (CSC) and eventually into cancer cells. CSCs are hypothesized to be key drivers of cancer cells and apparent drug resistance to the current anticancer drugs. Therefore, a drug that can kill the CSC within 72 hours can open a new window of success for stem cell therapy for treating severe diseases to a much simpler disorders such as baldness. Herein, we present the application of the recently reported ID-Checker technology (Journal of Medicinal Chemistry 2022 65 (19), 12883-12894) for killing CSC. ID-Checker possesses a glucose tag that ensures its highly specific absorption and macroscale delivery of anticancer agents into the CSCs through GLUT channels. ID-Checker kills the cancer cells within 72 hours. ID-Checker inhibits the microtubule formation and GLUT channel deployment in 6 h and kills the CSCs without damaging normal cells. Citation Format: Keum-soo Song, Satish Balasaheb Nimse, Taisun Kim. Killing cancer stem cells in 72 hours can cure breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2712.
Abstract 6526: Investigation levels of trace elements in breast cancer types using laser spectroscopic techniques
Authors: Ola Sayed Ahmed, hisham imam
Journal: Cancer Research (2023)

Abstract Breast cancer (BC) is the 2nd leading cause of death from cancer in women. Women have a lifetime risk of breast cancer of around 31%, which makes it the first most common malignancy in women. Diagnosing cancer and classifying its types is a complex process that relies heavily on sample analysis. Early detection of cancer diseases is one of the important and main factors in determining treatment and saving many patients before the disease worsens and reaches dangerous stages. Alterations in the levels of trace elements have been observed in breast cancer (BC) patients. However, the relationships between these alterations and the metabolic and clinical consequences of BC are unknown. The aim of the present work is to study in vitro possibilities and the effectiveness of introducing an efficient optical spectroscopic technique such as LIBS for the identification types of breast cancer, as well as determining the disease grade and severity. The ultimate goal of this work is to investigate the concentrations of several trace elements in BC patients, and their relationships with the molecular subtypes of tumors. The atomic transition of the neutral element lines of Fe, Al, Na, Ca, K, V, Co and Pb was chosen to determine the trace element levels of four breast cancer types. We found that the measured average level of trace elements can differentiate between different types of breast cancer. Citation Format: Ola Sayed Ahmed, hisham imam. Investigation levels of trace elements in breast cancer types using laser spectroscopic techniques [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6526.